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Amygdala connectivity predicts ketamine treatment response

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Re: Amygdala connectivity predicts ketamine treatment response

#31

Post by csnover »

chimeracoder wrote: post #20
mahathu wrote: post #18

Earlier quoted context omitted.

> (In fact, most studies focus on recreational users who are using near-clinical levels, which is an order of magnitude more than the typical recreational dose, and doing so with regularity). Is that so? For ambien it's the opposite, usually the recreational dosage can be a lot higher for some users than a clinical dosage (5 or 10mg)

> Is that so? For ambien it's the opposite, usually the recreational dosage can be a lot higher for some users than a clinical dosage (5 or 10mg) Correct. What you are saying is true for almost all drugs: recreational doses are typically higher than clinical doses. Ketamine is the exception. The recreational dose for a ketamine-naive user[0] is somewhere between 5-20mg. The clinical dose for depression is 86mg (not a…

> Correct. What you are saying is true for almost all drugs: recreational doses are typically higher than clinical doses. Ketamine is the exception.

To clarify: my understanding is that ketamine acts as a dissociative hallucinogen at lower doses and an anaesthetic at higher doses, so taking a higher dose will just knock someone out instead of giving them the dissociative/hallucinogenic effects.

> The clinical dose for depression is 86mg (not a typo), which is sometimes doubled, and the clinical dose for anesthetic purposes (which is what ketamine is mostly used for) is between 500mg-1g. The latter is IM injection, so it's also much more bioavailable than the first two (ie, the effective dose differential is even higher).

Ketamine is normally dosed based on body weight[0]. For depression IV, the dose is 0.1–0.75mg/kg/40mins, most commonly 0.5mg/kg/40mins. Clinical use in IM seems to be less consistent, with some clinicians using the same range and others doubling it, so the 86mg could be used for a wide range of body weights.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023575/table/T...

[1] https://www.psychiatrist.com/jcp/depression/ketamine-for-dep...

Re: Amygdala connectivity predicts ketamine treatment response

#32

Post by curioussavage »

cmrdporcupine wrote: post #21
pgt wrote: post #12

Most Ketamine users are unaware that even occasional usage can cause untreatable ulcerative cystitis, a.k.a. Ketamine Bladder Syndrome. Ketamine thins the urothelium while increasing the collagen to smooth muscle ratio and exacerbating interstitial fibrosis. The syndrome is untreatable and causes serious problems down the line. One promising rat study from 2015 shows that EGCG (epigallocatechin gallate) extracted fro…

Thanks for bringing this up. It's super important. And also makes me why other drugs in this class (dissociatives) aren't being looked more aggressively. Dextromethorphan -- in common cough syrup -- is one example. It has other side effects (nausea, etc.) but doesn't have the bladder destructive issues associated with ketamine.

Auvelity, a drug that combines dextromethorphan and bupropion (included to keep the dextromethorphan in the system longer) was just made available this quarter.

Re: Amygdala connectivity predicts ketamine treatment response

#33

Post by klyrs »

jonnycomputer wrote: post #8
bheadmaster wrote: post #7

Earlier quoted context omitted.

This sounds really promising, but one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). When heroin was first discovered, it was hailed as a wonder-drug, and it was also considered an effective treatment for severe depression. However, after some time, people realized that its addictive properties and high range of potential tolerance make it backfire pretty badly after a certa…

Good question. Ketamine has been a party drug for quite a while now, and as far as I know, hasn't been shown to be particularly dependency-inducing, though low-dose ketamine over the long term might be ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236511/ ) Also, as far as I know, ketamine treatment isn't intended as an ongoing medication, like an SSRI, but as a treatment for acute episodes of depression. I might b…

Like cannabis, people who use ketamine as an escape/coping mechanism can become habitually addicted. Ketamine addicts exist; two of my friends fit this description. From their reports, the first month off of the drug is a white-knuckle experience. If any becomes available, they can't resist using it until it's gone.

A lack of physical dependence should not be interpreted as addiction-proof. Nobody is physically dependent on gambling, for example, but gambling addiction is prevalent.

Re: Amygdala connectivity predicts ketamine treatment response

#34

Post by robocat »

engined wrote: post #25
jonnycomputer wrote: post #8

Earlier quoted context omitted.

Good question. Ketamine has been a party drug for quite a while now, and as far as I know, hasn't been shown to be particularly dependency-inducing, though low-dose ketamine over the long term might be ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236511/ ) Also, as far as I know, ketamine treatment isn't intended as an ongoing medication, like an SSRI, but as a treatment for acute episodes of depression. I might b…

The WebMD article is referencing esketamine, also known as Spravato, which is an FDA authorized form of ketamine. It's generally indicated for longer-term use in patients with Treatment Resistant Depression (TRD), and has really good results on par with ketamine (IV or intramuscular). At Lumin Health, we treat about 80% of our patients with esketamine, and the rest with ketamine (generally only if they don't meet esk…

Any comments on https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr... - presumably the doubts Scott had have now been answered?

Re: Amygdala connectivity predicts ketamine treatment response

#35

Post by chimeracoder »

csnover wrote: post #31
chimeracoder wrote: post #20

Earlier quoted context omitted.

> Is that so? For ambien it's the opposite, usually the recreational dosage can be a lot higher for some users than a clinical dosage (5 or 10mg) Correct. What you are saying is true for almost all drugs: recreational doses are typically higher than clinical doses. Ketamine is the exception. The recreational dose for a ketamine-naive user[0] is somewhere between 5-20mg. The clinical dose for depression is 86mg (not a…

> Correct. What you are saying is true for almost all drugs: recreational doses are typically higher than clinical doses. Ketamine is the exception. To clarify: my understanding is that ketamine acts as a dissociative hallucinogen at lower doses and an anaesthetic at higher doses, so taking a higher dose will just knock someone out instead of giving them the dissociative/hallucinogenic effects. > The clinical dose fo…

> Ketamine is normally dosed based on body weight[0]. For depression IV, the dose is 0.1–0.75mg/kg/40mins, most commonly 0.5mg/kg/40mins

If we're being specific, the FDA-approved treatment of ketamine for depression is a fixed 84mg dose. It is not adjusted for body weight.

(I did invite irony by saying that it wasn't a typo - it's 84 and 56 for redoing, not 86 and 54).

Re: Amygdala connectivity predicts ketamine treatment response

#36

Post by oaktrout »

robocat wrote: post #34
engined wrote: post #25

Earlier quoted context omitted.

The WebMD article is referencing esketamine, also known as Spravato, which is an FDA authorized form of ketamine. It's generally indicated for longer-term use in patients with Treatment Resistant Depression (TRD), and has really good results on par with ketamine (IV or intramuscular). At Lumin Health, we treat about 80% of our patients with esketamine, and the rest with ketamine (generally only if they don't meet esk…

Any comments on https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr... - presumably the doubts Scott had have now been answered?

For those who don't want to read the article, the highlights for me were: 1) esketamine may not work as well as ketamine and 2) esketsmine was invented to make pharm companies money because they couldn't do it with ketamine.

Re: Amygdala connectivity predicts ketamine treatment response

#37

Post by chimeracoder »

bheadmaster wrote: post #30
chimeracoder wrote: post #19

Earlier quoted context omitted.

> one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). The fact that two drugs both can be used as an anesthetic doesn't tell you very much besides that, especially when comparing across different drug classes. For example, cocaine and novocaine are both anesthetics that belong to the same drug class, and yet they have radically different risk profiles, despite both being comm…

> It's a fallacy to assume that ketamine would be subject to the same issues as opiates just because both happen to be usable as anesthetics. Sure, but it's also a fallacy to assume that nothing bad can happen in the long-term just because it appears promising in the short-term. I wasn't saying it's gonna happen the same exact way as it did with heroin (of course it won't, it's not an opiate), I was just making an ex…

> Sure, but it's also a fallacy to assume that nothing bad can happen in the long-term just because it appears promising in the short-term.

Ketamime has already been widely used for decades, in much larger doses than whats being discussed. We're not talking "short-term" here.

> I was just making an example of a drug that happened to appear benign and promising, but have serious unforeseen consequences in the long term.

Even that is a misrepresentation of the history of heroin. I guess it could appear that way if you take the Bayers advertising materials at face value (but hopefully you're not doing that). The dangers of opiates - and of morphine derivatives specifically - were well established by the time heroin was released.

Re: Amygdala connectivity predicts ketamine treatment response

#38

Post by anonymousnotme »

MDMA and psilocybin (magic mushrooms) and both in later stages of research and could be approved by FDA. From what information that I have read, one treatment of magic mushrooms can have a profound impact for one's life time. As I understand it, ketamine treatments don't last that long, so one needs to continue them. As far as magic mushrooms being toxic, they can't find a limit where it is toxic. The biggest problem as I understand it is that one might have a bad trip that could cause something like PTSD; so proper screening and preparation is needed. Check out youtube videos: https://youtu.be/kxFTWk9lLDU, https://youtu.be/smBMn-CV9KE, https://youtu.be/SwMHr43fTqE, https://youtu.be/NGIP-3Q-p_s

Re: Amygdala connectivity predicts ketamine treatment response

#39

Post by chimeracoder »

DontchaKnowit wrote: post #26
chimeracoder wrote: post #19

Earlier quoted context omitted.

> one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). The fact that two drugs both can be used as an anesthetic doesn't tell you very much besides that, especially when comparing across different drug classes. For example, cocaine and novocaine are both anesthetics that belong to the same drug class, and yet they have radically different risk profiles, despite both being comm…

I dont think its a fallacy. Its definitely a consideration. Ever met an nmda receptor agonist addict? its real shit. It aint pretty. And ive definitely seen it done as a sort of depression-relief-addiction. Had a close friend who I found out had been drinking like 2 or 3 bottles of cough syrup (over the counter, dextromethorphan) daily. She had a hell of a time kicking it. Idk if she ever did. People on these type of…

> I dont think this is an idea that can be dismissed trivially as a fallacy.

"Opiates are dangerous and they are anesthetics; therefore ketamine is dangerous because it's an anesthetic" is, literally, a textbook logical fallacy.

If you'd like to argue that ketamine is dangerous based on some other reasoning, go ahead, but that doesn't change the fact that OP's logic is prima facie fallacious.

> Ever met an nmda receptor agonist addict?

I used to work in drug counseling, so, yes.

Re: Amygdala connectivity predicts ketamine treatment response

#40

Post by chimeracoder »

DontchaKnowit wrote: post #27

I dont understand why we arent looking into methoxetamine over ketamine. Or any of the derivatives with a stronger dose-response curve. DCK, O-PCE, etc. These all have similar chemical and psychoactive properties and the doses are orders of magnitude smaller ergo they dont completepy fuck your bladder up.

> the doses are orders of magnitude smaller ergo they dont completepy fuck your bladder up.

There is zero clinical evidence of bladder damage due to ketamine in the amounts used for clinical purposes.

Yes, there is evidence for bladder damage in heavy, chronic users, but none of that has been shown in therapeutic schedules, and there is very strong evidence against the existence of any such link in therapeutic schedules.

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